The importance of establishing the diagnosis of ulcerative colitis arises at two levels. Acute idiopathic ulcerative colitis of recent onset must be distinguished from a variety of disorders that mimic it. Second, ulcerative colitis must be distinguished from Crohn's disease. The distinction between ulcerative colitis and Crohn's disease carries important prognostic and therapeutic implications. Development of a convenient and reliable blood test which could aid in diagnosing ulcerative colitis and might parallel disease activity or predict and impending flare would be an important advance. In other immunologically mediated disorders, serum autoantibodies have been of major diagnostic use and have provided insights into the underlying disease pathogenesis. In some cases, autoantibodies have been used to reveal the molecular structure/function of intracellular molecules. The study of autoantibodies at the molecular and cellular level is now viewed as an important "bridge between the clinical and basic sciences". We have recently found a subset of anti-neutrophil cytoplasmic autoantibodies in the majority of patients with ulcerative colitis. This UC-related ANCA is distinct from the ANCA which was originally reported in patients with Wegener's granulomatosus, using the ELISA assay described. The goal of this project is to assess the clinical utility of ANCA as a disease marker for ulcerative colitis, establish the identity and characteristics of the neutrophil cytoplasmic antigen(s) to which ANCA is reactive, and to define the characteristics of the immunoglobulins which comprise ANCA. In addition to facilitating the development of a diagnostic marker of ulcerative colitis, these studies will provide information which will be critical for subsequent investigations of the immunologic mechanisms of production and regulation of ANCA.